Benzyl sulfonamide derivatives as rorc modulators

Abstract

Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, A, B, C, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.

What is claimed is: 
     
         1 . A compound of formula I: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts thereof, 
       wherein:
 A is a group of formula: (a); (b); (c); or (d): 
 
       
         
           
           
               
               
           
         
         B is a group of formula: (e); (f); (g) or (h): 
       
       
         
           
           
               
               
           
         
         C is a group of formula: (i); (j); (k); or (m): 
       
       
         
           
           
               
               
           
         
         m is 0 or 1; 
         n is from 0 to 3; 
         p is from 0 to 2; 
         q is from 0 to 3; 
         r is from 0 to 3; 
         s is from 0 to 2; 
         t is 0 or 1; 
         u is from 0 to 3; 
         R 1  is: hydrogen; or C 1-6 alkyl; 
         R 2  is: hydrogen; or C 1-6 alkyl; 
         R 3  is: C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; heterocyclyl; heterocyclyl-C 1-6 alkyl; phenyl-C 1-6 alkyl; or C 1-6 alkylsulfonyl, wherein the C 1-6 alkyl, C 3-6 cycloalkyl C 3-6 cycloalkyl-C 1-6 alkyl and phenyl-C 1-6 alkyl each may be optionally substituted one or more time with halo; 
         R 4  is: hydrogen; or C 1-6 alkyl; 
         R 5  is: hydrogen; or C 1-6 alkyl; 
         R 6  is: cyano; —(CH 2 ) v —NR a R b ; —(CH 2 ) v —S(O) w —R c ; —(CH 2 ) v —C(O)—NR a R b ; —(CH 2 ) v —S(O) w —NR a R b ; —(CH 2 ) v —NR d —C(O)—R c ; —(CH 2 ) v —NR d —C(O)—NR a R b ; or —(CH 2 ) v —NR d —S(O) w —R c , wherein:
 v is 0 or 1, 
 w is from 0 to 2; 
 R a  and R b  each independently is: hydrogen; or C 1-6 alkyl; 
 R c  is: C 1-6 alkyl; C 3-6 cycloalkyl; or C 3-6 cycloalkyl-C 1-6 alkyl; and 
 R d  is: hydrogen; or C 1-6 alkyl; 
 
         each R 7  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; cyano; halo-C 1-6 alkyl; hydroxy-C 1-6 alkyl; halo-C 1-6 alkoxy; or C 1-6 alkylsulfonyl; 
         R 8  is: C 1-6 alkyl; C 3-6 cycloalkyl; or C 3-6 cycloalkyl-C 1-6 alkyl; 
         R 9  is: hydrogen; or C 1-6 alkyl; 
         R 10  is: hydrogen; or C 1-6 alkyl; 
         R 11  is: hydrogen; hydroxy; cyano; —(CH 2 ) n —NR a R b ; —(CH 2 ) n —S(O) v —R c ; —(CH 2 ) n —C(O)—NR a R b ; —(CH 2 ) n —S(O) v —NR a R b ; —(CH 2 ) n —NR d —C(O)—R c ; —(CH 2 ) v —NR d —C(O)—NR a R b ; or —(CH 2 ) n —NR d —S(O) v —R c . 
         each R 12  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; cyano; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; or C 1-6 alkylsulfonyl; 
         each R 13  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; cyano; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; or C 1-6 alkylsulfonyl; 
         each R 14  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; cyano; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; or C 1-6 alkylsulfonyl; 
         R 15  is: C 1-6 alkyl; C 3-6 cycloalkyl; or C 3-6 cycloalkyl-C 1-6 alkyl; 
         R 16  is: hydrogen; or C 1-6 alkyl; 
         R 17  is: hydrogen; or C 1-6 alkyl; 
         each R 18  is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; cyano; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; or C 1-6 alkylsulfonyl; and 
         R 19  is C 1-6 alkyl; 
         provided that the compound is not N-isobutyl-N-[5-(3-methanesulfonyl-phenyl)-thiophen-2-ylmethyl]-C-phenyl-methanesulfonamide. 
       
     
     
         2 . The compound of  claim 1 , wherein C is a group of formula (i). 
     
     
         3 . The compound of  claim 2 , wherein A is a group of formula (a). 
     
     
         4 . The compound of  claim 3 , wherein B is a group of formula (e). 
     
     
         5 . The compound of  claim 3 , wherein B is a group of formula (f). 
     
     
         6 . The compound of  claim 3 , wherein m is 0. 
     
     
         7 . The compound of  claim 3 , wherein m is 1. 
     
     
         8 . The compound of  claim 3 , wherein R 1  and R 2  are hydrogen. 
     
     
         9 . The compound of  claim 3 , wherein R 4  and R 5  are hydrogen. 
     
     
         10 . The compound of  claim 3 , wherein R 3  is: C 1-6 alkyl; C 3-6 cycloalkyl; or C 3-6 cycloalkyl-C 1-6 alkyl; each of which may be optionally substituted one or more times with halo. 
     
     
         11 . The compound of  claim 3 , wherein R 3  is C 1-6 alkyl. 
     
     
         12 . The compound of  claim 3 , wherein R 3  is isobutyl. 
     
     
         13 . The compound of  claim 3 , wherein A is a group of formula (a1) or (a2): 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 13 , wherein R 6  is: —SO 2 —R c ; —(CH 2 ) n —C(O)—NR a R b ; —(CH 2 ) n —SO 2 —NR a R b ; —(CH 2 ) n —NR d —C(O)—R c ; or —(CH 2 ) n —NR d —SO 2 —R c . 
     
     
         15 . The compound of  claim 1 , wherein the compound is of formula II: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 1 , wherein the compound is of formula III: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 1 , wherein the compound is of formula IV: 
       
         
           
           
               
               
           
         
       
     
     
         18 . A composition comprising:
 (a) a pharmaceutically acceptable carrier; and   (b) a compound of  claim 1 .   
     
     
         19 . A method for treating arthritis, said method comprising administering to a subject in need thereof an effective amount of a compound of  claim 1 .